摘要
目的:探究加味香薷口服液治疗腹泻疾病的潜在机制。方法:通过网络药理学和分子对接技术预测加味香薷口服液抗腹泻的主要活性成分、靶点及信号通路,并对预测的结果进行体外实验验证。结果:网络药理学结果表明,加味香薷口服液通过槲皮素、木犀草素、大豆苷元等黄酮类化合物及β-谷甾醇、β-胡萝卜素作用于丝/苏氨酸蛋白激酶1(serine/threonine protein kinase 1,AKT1)、信号传导和转录激活因子3(signal transducer and activator of transcription 3,STAT3)、白细胞介素-6等核心靶蛋白密切参与腹泻症状的发展进程;依据分子对接数据,其关键化合物与核心靶蛋白间结合能力普遍较强;脂多糖诱导的IEC-6肠上皮细胞实验表明,与模型组相比,加味香薷口服液能提高细胞存活率(P<0.05),使炎症因子白细胞介素-1β、肿瘤坏死因子-α和白细胞介素-6分泌水平降低(P<0.05),白细胞介素-10水平上升(P<0.01),并与剂量呈依赖趋势;还能下调磷酸化AKT1、肿瘤蛋白p53和磷酸化传导及转录激活因子3蛋白表达(P<0.05),上调表皮生长因子受体蛋白表达(P<0.05)。结论:加味香薷口服液主要通过多靶点、多信号通路以有效缓解脂多糖诱导的腹泻,其机制可能与STAT3、AKT1等关联信号通路的持续激活、调控肠道炎症状态、细胞应激反应有关。
OBJECTIVE To explore the potential mechanism of Jiawei Xiangru Oral Liquid(JWXR-OL)in the treatment of diarrhea.METHODS Network pharmacology and molecular docking technology were used to predict the major active ingredi-ents,targets,and signaling pathways of JWXR-OL against diarrhea.In vitro tests were conducted to confirm the predicted out-comes.RESULTS The results of network pharmacology indicated that JWXR-OL treated diarrhea by acting on core target pro-teins such as serine/threonine protein kinase 1(AKT1),signal transducer and activator of transcription 3(STAT3),interleukin-6 through flavonoids such as quercetin,luteolin,and daidzein,as well as β-sitosterol and β-carotene.Based on the molecular dock ing data,the binding ability between key compounds of Elsholtzia Plus and core target proteins was generally strong.In vitro tests in lipopolysaccharide-induced intestinal epithelial cell line IEC-6 showed that JWXR-OL increased the cell viability compared with the model group(P<0.05).It decreased the levels of inflammatory factors interleukin-1β,tumor necrosis factor-α and interleu-kint-6 levels(P<0.05),and increased interleukin-10 in a dose-dependent manner(P<0.01).It also down-regulated phosphory-lated protein kinase AKT1,tumor protein p53,and phosphorylated STAT3 protein expression(P<0.05),and up-regulated epi-dermal growth factor receptor protein expression(P<0.05).CONCLUSION JWXR-OL effectively alleviates diarrhea mainly through multi-target and multi-signaling pathways by continuously activating signaling pathways associated with STAT3 and AKT1,and regulating intestinal inflammatory status and cellular stress response.
作者
卢茂芳
李小兰
罗琳
李玉丽
王小青
梅秋兰
陈丹
李柯
LU Maofang;LI Xiaolan;LUO Lin;LI Yuli;WANG Xiaoqing;MEI Qiulan;CHEN Dan;LI Ke(School of Pharmacy,Hunan University of Chinese Medicine,Hunan Changsha 410208,China;Innovative Medicine Institute of Traditional Chinese Medicine,Hunan Academy of Chinese Medicine,Hunan Changsha 410013,China;Hunan Drug Safety Evaluation Research Center,Hunan Changsha 410331,China;Institute of Medical Technology,Xiangtan Medicine&Health Vocational College,Hunan Xiangtan 411102,China)
出处
《中国医院药学杂志》
北大核心
2025年第18期2085-2091,共7页
Chinese Journal of Hospital Pharmacy
基金
国家自然科学基金项目(编号:81804193)
湖南中医药大学研究生创新课题项目(编号:2024CX069)
湖南省教育厅科学研究项目(编号:23C0155)。
